US6100274AExpiredUtility

8-chloro-6,11-dihydro-11- ](4-piperidylidine)-5H-benzo[5,6]cyclohepta[1,2-bpyridine oral compositions

69
Assignee: SCHERING CORPPriority: Jul 7, 1999Filed: Jul 7, 1999Granted: Aug 8, 2000
Est. expiryJul 7, 2019(expired)· nominal 20-yr term from priority
Inventors:Jim H. Kou
A61K 9/2009A61K 31/4545A61K 9/2059
69
PatentIndex Score
32
Cited by
154
References
40
Claims

Abstract

Stable pharmaceutical compositions containing 8-chloro-6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cycloheptic[1,2-b]pyridine("DCL") and a DCL protective amount of a pharmaceutically acceptable basic salt such as calcium dibasic phosphate and an amount of at least one disintegrant, preferably two disintegrates such as microcrystalline cellulose and starch sufficient to provide dissolution of at least about 80% by weight of the pharmaceutical composition in about 45 minutes and suitable for oral administration to treat allergic reactions in mammals such as man are disclosed.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A pharmaceutical composition for oral administration comprising an anti-allergic effective amount of descarbonylethoxy-loratadine in a pharmaceutically acceptable carrier medium comprising a DCL-protective amount of a pharmaceutically acceptable basic salt and at least one pharmaceutically acceptable disintegrant. 
     
     
       2. The pharmaceutical composition of claim 1 wherein the at least one pharmaceutically acceptable disintegrant is in an amount sufficient to provide dissolution of at least 80% by weight of the pharmaceutical composition in about 45 minutes. 
     
     
       3. The pharmaceutical composition of claim 1 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to said disintegrant is in the range of about 1:1 to 2:1. 
     
     
       4. The pharmaceutical composition of claim 1 wherein the pharmaceutically acceptable basic salt is a calcium, magnesium or aluminum salt, or mixtures thereof. 
     
     
       5. The pharmaceutical composition of claim 1 wherein the pharmaceutically acceptable basic salt is a calcium phosphate salt. 
     
     
       6. The pharmaceutical composition of claim 1 wherein the pharmaceutically acceptable carrier medium is substantially free of acidic excipients. 
     
     
       7. A pharmaceutical composition of claim 1 which contains less than about 1% by weight of N-formyldescarbonylethoxyloratadine after storage at about 25° C. and about 60% relative humidity for at least 24 months. 
     
     
       8. The pharmaceutical composition of claim 1 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to the anti-allergic effective amount descarbonylethoxyloratadine is the range of about 5:1 to about 60:1. 
     
     
       9. A pharmaceutical composition for oral administration comprising an anti-allergic effective amount of descarbonylethoxy-loratadine in a pharmaceutically acceptable carrier medium comprising a DCL-protective amount of calcium dibasic phosphate, an amount of microcrystalline cellulose and of starch sufficient to provide dissolution of at least about 80% by weight of the pharmaceutical composition in about 45 minutes. 
     
     
       10. A pharmaceutical composition of claim 9 which contains less than about 1% by weight of N-formyldescarbonylethoxyloratadine after storage at about 25° C. and about 60% relative humidity for at least 24 months. 
     
     
       11. A pharmaceutical composition for oral administration comprising an anti-allergic effective amount of descarbonylethoxy-loratadine in a pharmaceutically acceptable carrier medium comprising a DCL-protective amount of calcium dibasic phosphate, an amount of microcrystalline cellulose and of starch sufficient to provide dissolution of at least 80% by weight of the pharmaceutical composition in about 45 minutes, and containing less than about 1% by weight of N-formyldescarbonyl-ethoxyloratadine after storage at about 25° C. and about 60% relative humidity for at least 24 months. 
     
     
       12. A pharmaceutical composition of claim 9 which comprises:   ______________________________________                                    
Ingredient           Amount (weight %)                                    
______________________________________                                    
Descarbonylethoxyloratadine                                               
                     about 0.5-15                                         
Calcium Dibasic Phosphate                                                 
Dihydrate USP                                 about 10-90                 
Microcrystalline Cellulose NF                                             
                              about 5-60                                  
Corn starch NF                               about 1-60                   
Talc USP                                           about                  
______________________________________                                    
                     0.5-20.                                              
     
     
     
       13. A pharmaceutical composition of claim 9 which comprises:   ______________________________________                                    
Ingredient           Amount (weight %)                                    
______________________________________                                    
Descarbonylethoxyloratadine                                               
                     about 0.5-15                                         
Calcium Dibasic Phosphate                                                 
                       about 45-60                                        
Dihydrate USP                                                             
Microcrystalline Cellulose NF                                             
                              about 20-40                                 
Corn starch NF                               about 5-15                   
Talc USP                                           about                  
______________________________________                                    
                     1-10.                                                
     
     
     
       14. A pharmaceutical composition of claim 11 wherein the amount of descarbonylethoxyloratadine is in the range of about 1 to about 10 weight percent. 
     
     
       15. A pharmaceutical composition of claim 9 which comprises:   ______________________________________                                    
Ingredient             Amount (weight %)                                  
______________________________________                                    
Descarbonylethoxyloratadine                                               
                       about 1-10                                         
Calcium Dibasic Phosphate Dihydrate USP                                   
                           about 50-56                                    
Microcrystalline Cellulose NF                                             
                                     about 25-35                          
Corn Starch NF                                      about 10-12           
Talc USP                                                  about           
______________________________________                                    
                       2-5.                                               
     
     
     
       16. The pharmaceutical composition of claim 1 which contains less than about 1% by weight of N-formyldescarbonylethoxyloratadine. 
     
     
       17. A pharmaceutical composition comprising an anti-allergic effective amount of descarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium comprising a DCL-protective amount of a pharmaceutically acceptable basic salt. 
     
     
       18. The pharmaceutical composition of claim 17 wherein said composition further comprises at least one pharmaceutically acceptable disintegrant. 
     
     
       19. The pharmaceutical composition of claim 18 wherein the at least one pharmaceutically acceptable disintegrant is in an amount sufficient to provide dissolution of at least about 80% by weight of the pharmaceutical composition in about 45 minutes. 
     
     
       20. The pharmaceutical composition of claim 19 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to said disintegrant is in the range of about 1:1 to 2:1. 
     
     
       21. The pharmaceutical composition of claim 18 wherein the pharmaceutically acceptable basic salt is a calcium, magnesium or aluminum salt, or mixtures thereof. 
     
     
       22. The pharmaceutical composition of claim 18 wherein the pharmaceutically acceptable basic salt is a calcium phosphate salt. 
     
     
       23. The pharmaceutical composition of claim 18 wherein the pharmaceutically acceptable carrier medium is substantially free of acidic excipients. 
     
     
       24. A pharmaceutical composition of claim 18 which contains less than about 1% by weight of N-formyldescarbonylethoxyloratadine. 
     
     
       25. The pharmaceutical composition of claim 18 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to the anti-allergic effective amount of descarbonylethoxyloratadine is the range of about 5:1 to about 60:1. 
     
     
       26. A pharmaceutical composition comprising an anti-allergic effective amount of descarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium wherein said composition contains less than about 1% by weight of N-formylDCL. 
     
     
       27. The pharmaceutical composition of claim 26 wherein said composition is adapted for oral administration. 
     
     
       28. The pharmaceutical composition of claim 26 wherein said composition has been stored at about 25° C. and about 60% relative humidity for at least 24 months. 
     
     
       29. The pharmaceutical composition of claim 1 wherein the w/w ratio of the DCL-protective amount of tje pharmaceutically acceptable basic salt to said disintegrant is in the range of about 1.5:1 to about 2:1. 
     
     
       30. The pharmaceutical composition of claim 1 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to said disintegrant is in the range of about 1.25:1 to about 1.75:1. 
     
     
       31. The pharmaceutical composition of claim 1 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to the anti-allergic effective amount descarbonylethoxyloratadine is the range of 7:1 to about 11:1. 
     
     
       32. The pharmaceutical composition of claim 1 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to the anti-allergic effective amount descarbonylethoxyloratadine is the range of about 10:1 to about 11:1. 
     
     
       33. The pharmaceutical composition of claim 19 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to said disintegrant is in the range of about 1.5:1 ; to about 2:1. 
     
     
       34. The pharmaceutical composition of claim 19 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to said disintegrant is in the range of about 1.25:1 to about 1.75:1. 
     
     
       35. The pharmaceutical composition of claim 18 wherein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to the anti-allergic effective amount of descarbonylethoxyloratadine is the range of about 7:1 to about 11:1. 
     
     
       36. The pharmaceutical composition of claim 18 whrein the w/w ratio of the DCL-protective amount of the pharmaceutically acceptable basic salt to the anti-allergic effective amount of descarbonylethoxyloratadine is the range of about 10:1 to about 11:1. 
     
     
       37. A pharmaceutical composition comprising an anti-allergic effective amount of descarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium wherein said composition contains less than about less than about 0.8% of N-formylDCL. 
     
     
       38. A pharmaceutical composition comprising an anti-allergic effective amount of descarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium wherein said composition contains less than about 0.6% of N-formylDCL. 
     
     
       39. A pharmaceutical composition comprising 5 mg of descarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium. 
     
     
       40. The pharmaceutical composition of claim 39 whrein said composition contains less than about 1% by weight of N-formylDCL.

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